Alterations of GABAergic Signaling in Autism Spectrum Disorders

Table 1

Main alterations of GABAergic signaling present in different animal models of ASDs. For the Rett syndrome, different genotypes are expressed in brackets.

Mouse model	Alterations in GABAergic signaling	Ref.
	Reduced levels of GAD65 and GAD67 (Viaat-Mecp2^−/y)	[75]
	Reduced inhibitory quantal size in layer 2/3 pyramidal neurons of the somatosensory cortex
Mecp 2-KO; (Rett syndrome)	The E/I balance is shifted to favor inhibition over excitation in cortical networks (Mecp2^2lox/x, Nestin-Cre)	[79]
	Reduced frequency of IPSC-based spontaneous rhythmic field potentials in the hippocampus (Mecp2^tm1.1Bird)	[80]
Fmr 1-KO; (X fragile)	Down regulation of GABAA-mediated tonic inhibition in the subiculum	[88]
	Reduced expression of α5 and 𝛿 GABAA receptor subunits in the subiculum
	Increased frequency of sIPSCs and mIPSCs in the striatum	[89]
	Reduction in amplitude and frequency of sIPSCs and mIPSCs	[90]
	Reduced GABAA-mediated tonic inhibition	[84–87]
	Reduced GABAergic innervation in the amygdala
	Reduced expression of GABAA receptor subunits
Gabrb 3 KO	The E/I balance is shifted to favor excitation over inhibition in cortical networks (EEG recordings)	[56]
Dlx1/Dlx2 KO	Abnormal cell migration
	Reduction in the number of GABAergic interneurons in the cortex, olfactory bulb and hippocampus	[97]
Reln-KO	Reduced level of GAD67	[103]
	Decreased GABA turnover
	Reduced expression of parvalbumin- and somatostatin-
En2-KO	positive GABAergic interneurons in the hippocampus	[115]
	Increased susceptibility to seizures
	Increased frequency of mIPSC
Nlg3 R451C KI	Increased level of VGAT and gephyrin	[106]
	Asymmetric reduction of PV positive basket cells across cortical hemispheres	[108]
valproic acid	The E/I balance is shifted to favor excitation over inhibition in the lateral amygdala (multi electrode arrays)	[114]
	Asymmetric reduction of PV positive basket cells across cortical hemispheres	[108]